A Study of Avelumab, Binimetinib and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant Solid Tumors

NCT03637491

About this Study

This Phase 1b/2 study will examine the effects of the study drugs, avelumab and binimetinib
given together (doublet) and in combination with talazoparib (triplet), in patients with
locally advanced or metastatic RAS-mutant solid tumors. The Phase 1b part of the study will
assess if the different study drugs can be given together safely and which doses to use for
further research. Phase 2 will test if the study treatments have an effect on tumor size and
growth, and gather more information about potential side effects.

The disease, disorder, syndrome, illness, or injury that is being studied.

Pancreatic Cancer, Non-Small Cell Lung Cancer, Cancer

Sex

Females and Males

Age

Pediatric Trials: 0-17 YearsAdult Trials: 18+ Years

18 + years

Inclusion criteria

The factors, or reasons, that allow a person to participate in a clinical study.

Show details

- Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid
tumors that are not amenable for treatment with curative intent as follows:

1. Stage IIIb/IV NSCLC with documented positive KRAS or NRAS mutation status as
determined using a validated test performed in a College of American Pathologists
(CAP)/Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (or
other comparable local or regional certification); or

2. Metastatic pancreatic ductal adenocarcinoma; or

3. Phase 2 only: other advanced solid tumors with documented positive KRAS or NRAS
mutation as determined using a validated test performed in a CAP/CLIA-certified
laboratory (or other comparable local or regional certification).

- Have had disease progression during or following at least 1 and not more than 2 prior
lines of treatment for advanced or metastatic disease.

- Patients with NSCLC must have previously received treatment with an anti-PD-1 or
anti-PD-L1 agent for advanced disease.

A Study of Avelumab, Binimetinib and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant Solid Tumors

Official Title ICMJE

A Phase 1b/2 Study To Evaluate Safety And Clinical Activity Of Avelumab In Combination With Binimetinib With Or Without Talazoparib In Patients With Locally Advanced Or Metastatic Ras-mutant Solid Tumors

Brief Summary

This Phase 1b/2 study will examine the effects of the study drugs, avelumab and binimetinib given together (doublet) and in combination with talazoparib (triplet), in patients with locally advanced or metastatic RAS-mutant solid tumors. The Phase 1b part of the study will assess if the different study drugs can be given together safely and which doses to use for further research. Phase 2 will test if the study treatments have an effect on tumor size and growth, and gather more information about potential side effects.

Detailed Description

This is a Phase 1b/2, open label, multi-center, safety, clinical activity, pharmacokinetic (PK), and pharmacodynamics (PD) study of avelumab in combination with binimetinib with or without talazoparib in adult patients with locally advanced or metastatic KRAS- or NRAS-mutant non-small cell lung cancer, pancreatic ductal adenocarcinoma, or other KRAS- or NRAS-mutant solid tumors.

The Phase 1b part of this study will initially assess the combination of avelumab and binimetinib (doublet) to determine a recommended dose for further investigation. Following this, the recommended dose for the combination of avelumab, binimetinib and talazoparib (triplet) will be determined. The recommended doses for the doublet and triplet combinations will be used in the Phase 2 part of the study, which will assess the safety and preliminary anti-tumor activity of the study treatments.

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Not yet recruiting

Estimated Enrollment ICMJE (submitted: August 16, 2018)

127

Original Estimated Enrollment ICMJE

Same as current

Estimated Study Completion Date

November 7, 2022

Estimated Primary Completion Date

May 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent as follows:

Stage IIIb/IV NSCLC with documented positive KRAS or NRAS mutation status as determined using a validated test performed in a College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (or other comparable local or regional certification); or

Metastatic pancreatic ductal adenocarcinoma; or

Phase 2 only: other advanced solid tumors with documented positive KRAS or NRAS mutation as determined using a validated test performed in a CAP/CLIA-certified laboratory (or other comparable local or regional certification).

Have had disease progression during or following at least 1 and not more than 2 prior lines of treatment for advanced or metastatic disease.

Patients with NSCLC must have previously received treatment with an anti-PD-1 or anti-PD-L1 agent for advanced disease.